We have obtained evidence that various epithelial cell lines secrete thermolabile factor(s) across the apical membrane that influence transepithelial permeability when applied to the basolateral membrane. Cells from the abeta amphibian kidney cell line were grown on Costar chambers until they reached confluence and the transepithelial electrical resistance (TER) was stabilized. When the basolateral surface of a confluent monolayer was exposed to apical medium, the TER increased progressively 16.5 +/- 1% within 5-20 minutes. After 40-60 minutes, the TER returned slowly to baseline values. An increase of 21.5 +/-3.2% was obtained when the apical medium was concentrated 20 times by ultrafiltration through a 30,000 MW cutoff membrane. This increase in TER was not observed when the apical medium was preheated at 65C for 10 minutes or when using the 30,000 MW filtrate. This increase of TER was observed both in the presence and absence of the serum used to supplement the fresh medium. This suggests that the component which promotes the increase of TER is secreted an slowly accumulated in the apical medium. Similar results were obtained with MDCK and Caco-2 cell lines. Furthermore, apical medium collected from one cell line promoted increase of TER when applied to the basal side of another cell line. These preliminary results indicate that a component of the apical medium promotes an increase in TER, restricting the passage of ions through tight junctions. Leakage of this apical component to the basolateral domain could be involved in a feedback mechanism controlling TER.